The present invention relates to a process for the preparation of 4-fluorophenols, and to certain novel 3-cyano-4-fluorophenols preparable thereby.
Fluorophenols are important chemical compounds as they are key intermediates in the synthesis of pharmaceutically or pesticidally active compounds, which in some cases are fluoroanalogues of naturally occurring substances. Fluorophenols are usually prepared by one of two routes:
(i) from chloronitrobenzenes via halogen exchange, reduction, diazotisation and hydrolysis, PA1 (ii) from bromofluorobenzenes by hydrolysis.
Since the range of chloronitrobenzenes which undergo the halogen exchange reaction is limited, only a few fluorophenols can be made by route (i) and then at considerable cost. The starting materials for the second route, (substituted-) bromofluorobenzenes, are not readily available. Another process is described in German Auslegeschrift No. 1213848, which specifically discloses the preparation of 4-fluoro-3,5-dimethoxyphenyl by the reduction of 4,4-difluoro-3,5-dimethoxycyclohexadienone using zinc powder and acetic acid. Apart from using the explosive fluoroperchlorate in the preparation of the latter starting material for 3,5-methoxyphenol, the process in its general aspect is limited to starting materials which are substituted with lower alkyl- or alkoxy groups at least one of the two positions meta to the keto group. In addition to use of zinc and acetic acid, the only other reduction conditions disclosed as suitable are chromium(II)-chloride, chromium(II)-acetate or a mixture of sodium iodide and acetic acid.